Functions of Fun30 Chromatin Remodeler in Regulating Cellular Resistance to Genotoxic Stress

The Saccharomyces cerevisiae Fun30 chromatin remodeler has recently been shown to facilitate long-range resection of DNA double strand break (DSB) ends, which proceeds homologous recombination (HR). This is believed to underlie the role of Fun30 in promoting cellular resistance to DSB inducing agent camptothecin. We show here that Fun30 also contributes to cellular resistance to genotoxins methyl methanesulfonate (MMS) and hydroxyurea (HU) that can stall the progression of DNA replication. We present evidence implicating DNA end resection in Fun30-dependent MMS-resistance. On the other hand, we show that Fun30 deletion suppresses the MMS- and HU-sensitivity of cells lacking the Rad5/Mms2/Ubc13-dependent error-free DNA damage tolerance mechanism. This suppression is not the result of a reduction in DNA end resection, and is dependent on the key HR component Rad51. We further show that Fun30 negatively regulates the recovery of rad5Δ mutant from MMS induced G2/M arrest. Therefore, Fun30 has two functions in DNA damage repair: one is the promotion of cellular resistance to genotoxic stress by aiding in DNA end resection, and the other is the negative regulation of a Rad51-dependent, DNA end resection-independent mechanism for countering replicative stress. The latter becomes manifest when Rad5 dependent DNA damage tolerance is impaired. In addition, we find that the putative ubiquitin-binding CUE domain of Fun30 serves to restrict the ability of Fun30 to hinder MMS- and HU-tolerance in the absence of Rad5.     

Monte Carlo Simulation-Based Health Risk Assessment of Heavy Metal Soil Pollution: A Case Study in the Qixia Mining Area,China

In recent years, heavy metal pollution accidents have occurred in many regions of China, and the public has become increasingly concerned about its health. Based on a U.S. Environmental Protection Agency model and using Monte Carlo simulation techniques, this article presents a procedure for health risk assessment of heavy metal pollution. A case study was conducted in the Qixia lead and zinc mining area. Based on the magnitude of heavy metal contamination in the mine factory, vicinal Qixia scenic site and village, the potential health risk calculated for a lifetime of exposure (through ingestion and dermal contact) was determined as the cumulative carcinogenic and non-carcinogenic risk for workers, tourists, and local residents (including children and adults), respectively. The risk assessment indicated that the carcinogenic risk is not significant. However, Pb poses a significant cumulative non-carcinogenic risk, which tends to be serious for workers. Additionally, local children are more vulnerable than adults to the risks associated with heavy metal contamination. Accordingly, risk alleviation and preventive measures should be taken, especially for children and workers.